Clinical Relevance of Isolated Lupus Anticoagulant Positivity in Patients with Thrombotic Antiphospholipid Syndrome

Abstract

Background: Patients positive for three types of antiphospholipid antibodies (aPLs) (triple positivity) have been identified at a high risk for thrombotic events. However, the clinical significance of isolated lupus anticoagulant (LAC) positivity is debated. Objectives: To investigate the clinical relevance of isolated LAC. Patients/Methods 456 patients were enrolled in this study; 66 antiphospholipid syndrome patients and 390 control patients. The control group existed of autoimmune patients (n=91), patients with thrombosis but without aPLs (n=127) and normal controls (n=172). The criteria LAC, anti-cardiolipin (anti-CL) and anti-beta2glycoprotein I (anti-β2GPI) IgG and IgM and the non-criteria IgA anti-CL and anti-β2GPI, anti-domain I (anti-DI) of β2GPI IgG and anti-phosphatidylserine/prothrombin (anti-PS/PT) IgG and IgM were detected according to the ISTH guidelines for solid phase assays. Results: 70 patients were positive for LAC, of which 44 were negative for both anti-β2GPI and anti-CL. We found that isolated LAC proved to be strongly associated with vascular thrombosis (Odds ratio (OR) (95% CI) 7.3 (3.3-16.1)), even better than triple positive samples (OR 4.3 (1.6-12.2)). The titers of the anti-PS/PT IgG and IgM were significantly higher in triple positivity samples compared to samples with isolated LAC positivity. The majority of single LAC positives were anti-PS/PT negative. We observed that LAC positivity was weaker in isolated LAC positive patients compared to LAC activity in triple positive patients. Conclusions: Isolated LAC was highly associated with thrombosis. The presence of anti-PS/PT could not explain LAC positivity in isolated LAC. Isolated LAC showed a weaker LAC activity compared to triple positive patients.

Clinical and laboratory characteristics of Brazilian versus non-Brazilian primary antiphospholipid syndrome patients in AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) clinical database and repository

“…It is widely known that LA is the aPL associated with the highest risk of thrombosis in APS patients [8,9]. In a recently published study, Yin et al analyzed 456 patients (66 APS patients vs. 390 controls) and found that isolated LA positivity was a strong predictor of vascular thrombosis (OR 7.3, CI95% 3.3-16.1), even better than triple positivity (OR 4.3, CI95% 1.6-12.2) [10]. Also, in previously published studies, LA, not triple positivity, was associated with a higher risk of thrombosis [11] and obstetric complications [12] in SLE patients.…”

“…9 CHU de Québec-Université Laval, Québec, QC, Canada. 10 Rheumatology Service, IMIBIC/Reina Sofia Hospital, University of Cordoba, Cordoba, Spain. 11 Rheumatology and Immunology Department, Peking University First Hospital, Beijing, China.…”

Role of antiphospholipid antibodies in the diagnosis of antiphospholipid syndrome

“…Isolated positivity of LA, in absence of aCL and aβ2GPI, is regarded as a lower risk factor [ 4 ]. We observed that LA positivity, expressed as normalized ratio, was weaker in isolated LA-positive patients compared with LA activity in triple-positive patients, suggesting that stronger LA better corresponds with a high risk profile [ 30 ]. Attempts have been made to quantify or measure LA by other methods such as thrombin generation assays [ [31] , [32] , [33] ].…”

“…Recently, a prospective observational study found that in a LA positive population the association between occurrence of thrombosis and inferior survival was independent of the detection of aCL and aβ2GPI [ 72 ]. A retrospective multicenter study illustrated that isolated LA proved to be strongly associated with vascular thrombosis even though with a weaker LA activity compared with LA activity in triple positive patients [ 30 ]. The majority of these patients was negative for aPS/PT (see also further on).…”

Use of Direct Oral Anticoagulants in Patients With Antiphospholipid Syndrome: A Systematic Review and Comparison of the International Guidelines

“…The thrombotic risk seems to be influenced by the clinical and immunological characteristics of patients with triple positive aPL patients having the highest thrombotic risk, estimated at 5.3% per year ( 11 , 12 ). However, the thrombotic potential of non-criteria aPL and the value of isolated IgM/LAC is still under investigation ( 13 – 15 ). Furthermore, a significant proportion of patients present a negativization of aPL during follow-up, but it is unclear if it parallels a reduction of thrombotic risk ( 16 ).…”